Nutraceuticals & Long COVID: What Clinical Science Supports (and What Doesn’t)

By Editorial Team -

Abstract

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms such as fatigue, dyspnea, cognitive impairment, and dysautonomia. Interest in nutraceuticals—dietary supplements, herbal extracts, and vitamins—has grown as potential adjuncts to symptom management. This review evaluates current clinical and preclinical evidence for commonly discussed nutraceuticals, including curcumin, N-acetylcysteine (NAC), omega-3 fatty acids, nattokinase, bromelain and probiotics, and contrasts them with established evidence-based clinical management. While some nutraceuticals demonstrate mechanistic plausibility for anti-inflammatory or antioxidant effects, high-quality clinical trial evidence supporting their efficacy in Long COVID is largely absent. Clinicians and patients should consider nutraceuticals as adjunctive therapy under supervision, prioritizing guideline-recommended interventions such as multidisciplinary care, rehabilitation, and symptom-targeted treatments.

Keywords: Long COVID, PASC, nutraceuticals, supplements, spike protein, curcumin, NAC, omega-3,  probiotics, clinical evidence.

Introduction

Long COVID affects a growing population worldwide, with persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. Pathophysiological mechanisms include chronic inflammation, endothelial and microvascular dysfunction, immune dysregulation, and residual viral antigens.

Given limited pharmacological interventions, interest in nutraceuticals has increased. Popularly cited candidates include curcumin, N-acetylcysteine (NAC), omega-3 fatty acids, probiotics, nattokinase, bromelain and vitamins D, C, and zinc. Despite mechanistic support, clinical trial evidence in Long COVID remains sparse.

Methods

A literature search was conducted in PubMed, PMC, and MEDLINE through January 2026. Keywords included “Long COVID,” “post-acute SARS-CoV-2 sequelae,” “nutraceuticals,” “curcumin,” “N-acetylcysteine,” “omega-3,” “probiotics,” and “vitamins.” Studies included human clinical trials, preclinical studies, systematic reviews, and guideline recommendations. Data were extracted on efficacy, safety, and evidence quality.

Results

1. Curcumin

  • Mechanistic Evidence: Modulates NF-kB and cytokine activity; may reduce inflammation.

  • Clinical Evidence: No high-quality randomized controlled trials (RCTs) demonstrating symptom improvement in Long COVID. Most evidence is preclinical or from acute COVID studies. (PMC Article)

2. N-Acetylcysteine (NAC)

  • Mechanistic Evidence: Antioxidant, precursor to glutathione; may reduce oxidative stress and inflammation.

  • Clinical Evidence: Limited human studies in Long COVID; mostly theoretical or extrapolated from acute respiratory distress contexts. (PMC Article)

3. Omega-3 Fatty Acids

  • Mechanistic Evidence: Anti-inflammatory properties; support endothelial and cardiovascular health.

  • Clinical Evidence: No Long COVID-specific RCTs; evidence extrapolated from other inflammatory conditions.

4. Probiotics and Prebiotics

  • Mechanistic Evidence: Potential modulation of gut microbiota and systemic immune response.

  • Clinical Evidence: No RCTs for Long COVID; some evidence from other viral illnesses suggests immune benefits.

5. Vitamins D, C, and Zinc

  • Mechanistic Evidence: Support immune function; potential antiviral roles.

  • Clinical Evidence: Observational studies link adequate levels to reduced severity in acute infection; direct evidence for Long COVID symptom mitigation is limited.

6. Nattokinase and bromelain

McCullough et al. published in 2023 (Journal of American Physicians and Surgeons) the first rationale for spike protein detoxification, called the McCullough Protocol Base Spike Detoxification: base spike detoxification, that holds considerable promise. 

Benefits: The protocol includes a natural triple-agent oral regimen of nattokinase, bromelain, and curcumin that provides four putative, primary mechanisms of action: 
  1. proteolytic degradation of spike protein, 
  2. inhibition of inflammation from spike protein and its fragments in tissues, 
  3. dissolution of microthrombi, and 
  4. anticoagulation.
Recommended Dosage: 
  1. Nattokinase 2000 FU (100 mg) twice a day
  2. Bromelain 500 mg once a day
  3. Nano/Liposomal Curcumin 500 mg twice a day
Evidence: Hulscher et al. Cureus, 2023. (PubMed)

Comparative Summary: Nutraceuticals and Clinical Evidence

  1. Curcumin, bromelain and nattokinase

    • Mechanistic plausibility: Anti-inflammatory, antioxidant

    • Clinical evidence: Limited; mostly preclinical

    • Status: Adjunctive consideration, not primary therapy

  2. N-Acetylcysteine (NAC)

    • Mechanistic plausibility: Antioxidant, glutathione precursor

    • Clinical evidence: Sparse; theoretical support only

    • Status: May be used adjunctively with supervision

  3. Omega-3 Fatty Acids

    • Mechanistic plausibility: Anti-inflammatory, endothelial support

    • Clinical evidence: Extrapolated from other conditions; no Long COVID trials

    • Status: Supportive role only, not proven

  4. Probiotics/Prebiotics

    • Mechanistic plausibility: Gut-immune modulation

    • Clinical evidence: No Long COVID-specific trials

    • Status: Potential supportive adjunct

  5. Vitamins D, C, Zinc

    • Mechanistic plausibility: Immune support

    • Clinical evidence: Observational; no RCTs demonstrating Long COVID benefit

    • Status: Safe adjunctive support when deficient, not primary treatment

Discussion

Nutraceuticals may offer theoretical benefits for Long COVID due to their anti-inflammatory, antioxidant, and immunomodulatory properties. However, high-quality clinical evidence is largely absent.

  • Safety: Generally safe when used within recommended doses, but interactions with medications or exacerbation of comorbidities are possible.

  • Guideline Alignment: Evidence-based management emphasizes multidisciplinary evaluation, rehabilitation, and symptom-focused care, not nutraceuticals as primary therapy (PMC Article).

  • Clinical Recommendation: Nutraceuticals can be considered adjunctively under supervision, particularly for patients seeking supportive interventions.

Conclusion

  • Nutraceuticals such as curcumin, NAC, omega-3 fatty acids, probiotics, and vitamins have mechanistic plausibility but lack high-quality clinical evidence for Long COVID.

  • Evidence-based management—including multidisciplinary evaluation, symptom-targeted therapy, and rehabilitation—remains standard of care.

  • Supplements may be used cautiously as adjunctive therapy but should not replace established medical interventions.

References

  1. Curcumin as an Anti-Inflammatory Agent. PMC. (Link)

  2. N-Acetylcysteine and COVID-19 Mechanistic Evidence. PMC. (Link)

  3. Long COVID: Evidence-Based Guidelines for Diagnosis and Management. PMC. (Link)

  4. Long COVID: Current Insights and Future Directions. MDPI. (Link)

  5. Long COVID — Wikipedia Summary of Evidence-Based Treatment. (Link)

  6. Long COVID in 2026: Integrative Biological Insights and Therapeutic Considerations. COVID Advisor (Link)

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